Intravenous (i.v.) administration of 300 micrograms methylated BSA (
mBSA) to C57-Black mice with unilateral
antigen-induced
arthritis (AIA) of 4-6 weeks duration resulted in a reproducible flare-up of ongoing
arthritis without signs of
inflammation in the contralateral non-arthritic knee joint. In the present study we investigated characteristics of the flare-up phenomenon using histological grading and 99mtechnetium
pertechnetate uptake measurements to detect and quantitate knee joint
inflammation. At 6 h after intravenous
mBSA administration flare-up of
arthritis was demonstrable, showing histological characteristics of acute joint
inflammation; later this progressed to chronic stages, but the inflammatory stage did not return to baseline values up to day 9 after i.v. challenge. Varying the dose of i.v.
mBSA from 2 to 1000 micrograms showed that 10 micrograms was sufficient to elicit the phenomenon and also that the latter is dose-dependent. Using mice immunized with both
mBSA and methylated HGG (
mHGG) with either
mBSA or
mHGG-induced
arthritis, we could show that 4-6 weeks after
arthritis induction the flare-up phenomenon is
antigen specific.
Intra-articular injection of as little as 10 ng of
mBSA resulted in exacerbation of
inflammation in joints with chronic
mBSA-induced
arthritis, but induced no
inflammation in the contralateral non-arthritic knee joints, indicating local
hypersensitivity in the former joints. The flare-up phenomenon may be due to local hyper-reactivity of chronically inflamed joints to minimal amounts of circulating
antigen entering the joint.